Previous studies have demonstrated that neurotransmission in the rat septohippocampal cholinergic system, which has been implicated in memory functions, undergoes adaptive changes in response to stressful stimuli. During aging, many neurons in this system degenerate and may cause memory loss. It is possible that hyperreactivity to stressful stimuli can also accelerate neuron degeneration in this system. Our aim in this project is to learn: (a) whether or not the characteristic stress-induced adaptive changes in cholinergic neurons are altered in aged rats; (b) how age-related changes in neurotransmitter systems that converge in the septum influence the septohippocampal cholinergic system; and (c) how age-related changes in the regulation of glucocorticoid hormonal system effect the septohippocampal cholinergic system. The results so far indicate that age-related degeneration of cholinergic neurons is accompanied by compensatory-changes in their neighboring-neurons to prevent the loss of cholinergic neurotransmission, and that high glucocorticoid levels can accelerate the degeneration rate of cholinergic neurons. Studies are in progress to pursue these objectives further.